Bipolar disorder is a psychiatric condition associated with alternating episodes of depression and mania or hypomania. Depression is a period of over two weeks of persistent sadness, lack of pleasure in activities previously enjoyed, negative thoughts, changes in terms of energy level, appetite, and sleep. In severe cases, suicidal thoughts or psychosis may occur.
During periods of mania or its less severe version, hypomania, individuals experience the opposite of depression: exalted mood, giddiness, increased energy, lack of need for sleep and highly unusual ideas and behavior which can result in significant risk-taking and disconnection from reality. The causes of bipolar disorder are the subject of much research as there is no biological measure, brain scan, or blood test that can currently assist reliably with diagnosis and treatment.
Furthermore, accumulating studies are showing that there is a substantially increased risk of heart disease and stroke among people with bipolar disorder. They also have an onset of heart disease that is up to 14 years earlier than the general population and are twice as likely to die from heart disease or stroke than those without bipolar disorder. This elevated risk extends beyond what can be explained by medications or by lifestyle factors such as diet and exercise. It is not yet clear what other factors contribute to the excess burden of these vascular disorders. Measurements of blood flow in the brain could potentially inform our understanding of the bipolar-vascular link.
Cerebral blood flow refers to the amount of blood that is delivered to the brain. As an organ with high energy demands and low energy reserves, the brain is dependent on constant blood supply for oxygen and glucose. The brain regions which are active at any given moment receive the most blood supply. Cerebral blood flow can be examined in different ways using neuroimaging techniques. Scans can use technologies from nuclear medicine (such as single photon emission computerized tomography, or SPECT) requiring the injection of intravenous contrast to visualize the vessels, or more recent technology using magnetic resonance imaging (MRI) in which the water molecules in the blood are themselves used to visualize the blood vessels.
We set out to identify and compare the findings of all the prior studies that have examined cerebral blood flow in people with bipolar disorder. Our search found a total of 33 relevant articles, with 508 participants with bipolar disorder and 538 comparison participants. Studies used a variety of methods and looked at bipolar disorder participants in different mood states while resting and as they were performing cognitive or emotional tasks in the scanner.
The majority of studies found that bipolar disorder participants have lower blood flow when in the midst of an episode of depression or mania, although some studies found different results. Lower blood flow in comparison to healthy controls was found in brain regions in the frontal (responsible for emotions, judgment, and cognition), parietal (responsible for language and sensory information) and temporal (responsible for memory) lobes. In those studies that have looked at cerebral blood flow during a task, the normal increase in blood flow associated with a cognitive task in healthy participants was smaller in those with bipolar disorder or occurred in different brain regions. Only a few studies compared subjects with bipolar disorder to those with major depressive disorder (i.e. depression episodes that do not alternate with manic episodes) and did not identify significant differences.
The findings of lower blood flow in regions associated with emotional control and interplay between emotions and cognition may be due to several factors. First, prior studies of brain function in bipolar disorder found decreased activity in similar regions, which could signify that decreased blood flow could be related to less activity in those regions. It is difficult to know the exact direction of this association, as brain regions could be less active due to inadequate local blood flow, or less blood flow could be needed due to decreased activity. Similarly, some of the regions we found to have lower blood flow in this review were found to be smaller in terms of volume in other studies looking at brain structure. From studies in a healthy population or in participants with vascular problems, we know that lower brain size in a given region is associated with lower blood flow in that region. Again the direction of this relationship is not known.
The question arises as to what other factors may explain the link between bipolar disorder and abnormal cerebral blood flow. It is known that markers of inflammation in the blood are abnormally elevated among people with bipolar disorder, particularly during episodes of depression and/or mania. Over time, elevated inflammation is known to damage blood vessels. Most likely, abnormal cerebral blood flow is the result of a combination of factors, including genetics, vascular risk factors (e.g. high blood pressure or cholesterol), and increased inflammation and other factors.
There are several limitations to this review. Many of the included studies have a small number of subjects. The studies are also difficult to compare amongst themselves due to the different techniques employed and to differences between participants (depressed or hypomanic, medication taken). There is also only one study in adolescents and no study specifically in older adults and it is therefore not possible to infer how blood flow evolves over time in bipolar disorder. In addition, no study has directly compared blood flow with markers of inflammation or vascular health among people with bipolar disorder, limiting our understanding of factors impacting cerebral blood flow that are unique to bipolar disorder (and likely other brain disorders).
Nonetheless, we believe cerebral blood flow to be a subject of interest for future studies. Future studies should look at cerebral blood flow in bipolar disorder not only during different mood episodes but also at different stages of their illness and different ages. More information is needed regarding the intersection of cerebral blood flow with other disease processes (such as inflammation) and other brain measures (such as structural and functional imaging). Do people with bipolar disorder differ from other people in terms of the link between cerebral blood flow and vascular risk factors? Finally, can cerebral blood flow abnormalities be used as a treatment target for bipolar disorder in the future? As of now, we don’t know whether normalizing cerebral blood flow would have an impact on mood symptoms of bipolar disorder. Based on what we know so far, this would be a worthwhile hypothesis to test out.
Published by Simina Toma
Sunnybrook Health Sciences Centre and the University of Toronto
These findings are described in the article entitled Cerebral blood flow in bipolar disorder: A systematic review, recently published in the Journal of Affective Disorders (Journal of Affective Disorders 241 (2018) 505-513). This work was conducted by Simina Toma, Bradley J. MacIntosh, Walter Swardfager, and Benjamin I. Goldstein from Sunnybrook Health Sciences Centre and the University of Toronto.
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